In the present study, three series of 35 pyridine-based stilbenes include 10 new compounds prepared by Horner-Wadsworth-Emmons (HWE) reaction were assayed for cytotoxic activities toward two tumoral cell lines (K562 and MDA-MB-231) and one non-tumoral cell line (L-02). The bioassay results indicated that hybrid stilbenes formed at the C-3 position of pyridine displayed stronger antiproliferative activities against K562 cells and C-4 pyridine-based stilbenes showed broad-spectrum cytotoxic effects. Among them, C-3 pyridine-based stilbene